Efficacy and Safety Study of TLC388 to Advanced Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

Official title:

An Open-Label, Single-Arm, Two-Stage, Multi-Centre Phase II Study to Evaluate the Efficacy and Safety of TLC388 as Second-line Treatment in Subjects With Advanced Hepatocellular Carcinoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02267213
• Other study ID #: TLC388.4
• Status: Terminated
• Phase: Phase 2
• Start date: April 10, 2014
• Est. completion date: July 9, 2015

Study information

• Verified date: February 2019
• Source: Taiwan Liposome Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the safety and efficacy of TLC388 (Lipotecan) as a second line treatment in subjects with advanced Hepatocellular Carcinoma.

Description:

A Phase II, open-label, single-arm, two-stage, multicenter study to evaluate the efficacy and safety of Lipotecan® monotherapy in patients with advanced hepatocellular carcinoma (HCC) and had failed sorafenib treatment due to sorafenib intolerance or radiographic progressive disease (PD).

Eligible patients received 40 mg/m2 of Lipotecan®, given as a 30-minute (+3 minutes) intravenous infusion, on Days 1, 8, and 15 of a 28-day cycle for maximum 6 cycles. Inter-cycle and intra-cycle dose delays were allowed within 21 days of the scheduled date to be reduced to 35 mg/m2 and further to 30 mg/m2 if a treatment-related adverse event (TRAE) met the criteria for dose reduction.

Tumor response was assessed every 2 cycles until Cycle 6, or at the early termination according to RECIST Version 1.1 judged by site investigator. The favorable response of CR, PR or SD would be confirmed within 28-35 days. Safety evaluations were conducted on a weekly basis from the day study treatment administered throughout each cycle.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 29
• Est. completion date: July 9, 2015
• Est. primary completion date: July 9, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Radiological diagnosis of hepatic tumor(s) by contrast-enhanced study

• Subjects with advanced HCC who are not eligible for surgical resection or loco-regional therapy.

• Subjects with sorafenib treatment failure due to sorafenib intolerance or radiographic PD (as per RECIST v1.1). Prior sorafenib use should be = 400 mg/day for at least 14 days.

• Eastern Cooperative Oncology Group (ECOG) performance status of = 1

• Child Pugh Score = 6;

• A life expectancy of at least 12 weeks or more

Exclusion Criteria:

• Subjects who have received any systemic target therapy or systemic chemotherapy other than sorafenib for the treatment of HCC.

• Subjects who have received sorafenib within 2 weeks prior to the initiation of the treatment dose, or have any sorafenib-related toxicities not yet resolved to grade 1 or baseline.

• Subjects who have undergone liver transplantation surgery.

• Major surgery within 4 weeks prior to the initiation of the treatment dose (excluding implantation of the intravenous infusion device). Percutaneous liver puncture within 2 weeks prior to the initiation of the treatment dose.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Drug:
• Lipotecan
Administer 40mg Lipotecan at D1, D8, D15 of each cycle.

Locations

Country	Name	City	State
China	307 Hospital of PLA	Beijin
China	Nanjing Bayi Hospital	Nanjing
China	Shanghai Cancer Hospital, Fudan University	Shanghai
China	Zhongshan Hospital, Fudan University	Shanghai
Taiwan	Chiayi Chang Gung Memorial Hosipital	Chiayi City
Taiwan	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hosipital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hosipital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Mackay Memorial Hosipital	Taipei City
Taiwan	LinKou Chang Gung Memorial Hosipital	Taoyuan

Sponsors (1)

Lead Sponsor	Collaborator
Taiwan Liposome Company

Countries where clinical trial is conducted

China,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease Control Rate (DCR)	DCR (Disease control rate), the percentage of subjects with a best response rate of complete response (CR), partial response (PR), or stable disease (SD)	8 weeks from initial treatment
Secondary	Objective response rate (ORR; where ORR= CR rate + PR rate)	ORR (Objective response rate)	8 weeks(Cycle 2), 16 weeks (Cycle 4), 24 weeks (Cycle 6) from initial treatment and/or Early termination (before 24 weeks)
Secondary	Duration of Disease control (DDC)	Duration of disease control is defined as the time from first documented evidence of CR or PR or SD until the first documentation of PD or death due to any cause, whichever occurs first.	2 months (Cycle 2), 4 months (Cycle 4) and 6 months (Cycle 6) and/or Early termination (before 6 months)
Secondary	Time to Progression (TTP)	Time to tumor progression is defined as the time from first study drug administration until the first documentation of tumor progression.	2 months (Cycle 2), 4 months (Cycle 4) and 6 months (Cycle 6) and/or Early termination (before 6 months)
Secondary	Progression Free Survival (PFS)	The PFS is defined as the time from the first dose to the date of progression or death, whichever occurs first, and subjects with no evidence of progression or death at the time of study completion (the analysis cut-off date) or who are receiving any further anticancer therapy will be censored on the date of the last adequate tumor assessment.	2 months (Cycle 2), 4 months (Cycle 4) and 6 months (Cycle 6) and/or Early termination (before 6 months)
Secondary	Overall Survival (OS)	The OS is defined as the time from the first dose to the date of death, regardless of the cause of death, and subjects who are alive at the time of study completion will be censored at the last known alive date. Subjects who commence treatment with another anticancer agent will be censored at the day before the other anticancer treatment starts.	Up to 2 years from the last treatment of the last subject
Secondary	Change of Tumor markers/Bio-markers	tumor markers/biomarkers, including a-fetoprotein (AFP), vascular endothelial growth factor (VEGF), transforming growth factor-ß1 (TGF-ß1), and interleukin-6 (IL-6)	Baseline, the first dose (Cycle 1 Day 1), 2 months(C2D1), 3 months(C3D1), 4 months(C4D1), 5 months(C5D1), 6 months(C6D1) and/or Early termination (before 6 months)
Secondary	AEs	Serious/ Adverse Events	From ICF singed to 30 days after EOT
Secondary	Vital signs	evaluate at every administration and the end of treatment	Baseline, first treatment(C1D1), 1, 2, 4, 5, 6, 8, 9, 10, 12, 13, 14, 16, 17, 18, 20, 21, 22 weeks from the first treatment and/or Early termination (up to 24 weeks)
Secondary	Resting 12-lead ECGs	12-Lead ECGs	Baseline, the first dose (Cycle 1 Day 1), 2 months(C2D1), 3 months(C3D1), 4 months(C4D1), 5 months(C5D1), 6 months(C6D1) and/or Early termination (before 6 months)
Secondary	Hematology	evaluate at every administration and the end of treatment	Baseline, first treatment(C1D1), 1, 2, 4, 5, 6, 8, 9, 10, 12, 13, 14, 16, 17, 18, 20, 21, 22 weeks from the first treatment and/or Early termination (up to 24 weeks)
Secondary	Clinical chemistry	evaluate at every administration and the end of treatment	Baseline, first treatment(C1D1), 1, 2, 4, 5, 6, 8, 9, 10, 12, 13, 14, 16, 17, 18, 20, 21, 22 weeks from the first treatment and/or Early termination (up to 24 weeks)
Secondary	Urinalysis data	Urinalysis Lab Values	The first dose (Cycle 1 Day 1), 2 months(C2D1), 3 months(C3D1), 4 months(C4D1), 5 months(C5D1), 6 months(C6D1) and/or Early termination (before 6 months)
Secondary	PK parameters, including AUC, Cmax and Tmax of S,S-TLC388, S,R-TLC388, metabolites TLC-U1, TLC-U2, and topotecan	PK parameters	0, 15, 29, 33, 40, 50 minutes, and 1, 1.5, 2, 4, 8 hour after the start of infusion of the 1st treatment and 1 week (2nd treatment); 0, 29 minutes and 4 hour after the start of infusion of the 3, 5, 6 and 7 weeks (the 3rd, 4th, 5th, 6th treatment)